MAGELLAN: Rivaroxaban efficacy comparable to enoxaparin in acutely ill

Issue: May 2011

American College of Cardiology 60th Annual Scientific Sessions

NEW ORLEANS — Results of the MAGELLAN trial demonstrate that, when used as thromboprophylaxis in acutely ill hospital patients, rivaroxaban was not inferior to enoxaparin when used short-term and was slightly superior to enoxaparin followed by placebo when used long-term. However, compared with enoxaparin, rivaroxaban was associated with an increased rate of bleeding.

“Not only did we show that rivaroxaban was effective in this setting, but we also showed that at 35 days patients are still at risk for venous thrombosis,” Alexander T. Cohen, MD, of the department of surgery at King's College Hospital, London, said during a press conference. “We had a 5.7% frequency in the control arm, which was higher than the benchmark data of about 4%.”

The phase 3 trial compared oral rivaroxaban with subcutaneous enoxaparin (Lovenox, Sanofi-Aventis) in patients admitted to the hospital for acute HF, acute infectious disease and acute respiratory insufficiency or other acute medical conditions. Patients from 52 countries (n=8,101) were randomly assigned to rivaroxaban for 35 days (n=4,050) or enoxaparin for 10 days (n=4,051); both groups received placebo. The primary endpoint was a composite of asymptomatic proximal deep vein thrombosis, symptomatic deep vein thrombosis, symptomatic non-fatal pulmonary embolism and venous thromboembolism-related death. The primary safety outcome was a composite of treatment-related major bleeding and clinically relevant non-major bleeding.

At 10-days follow-up, the primary endpoint was similar between both groups: 2.7% of patients in both arms experienced the primary endpoint (relative risk ratio=0.968; P=.0025 for non-inferiority, one-sided).

At 35-days follow-up, researchers documented superiority in the rivaroxaban arm compared with enoxaparin followed by placebo: 4.4% of patients in the rivaroxaban group experienced the primary endpoint vs. 5.7% in the enoxaparin group (relative RR=0.771; P=.0211 for superiority, two-sided).

Conversely, enoxaparin was superior to rivaroxaban in reducing the rate of bleeding at both 10 and 35 days: at 10-days 1.2% of patients in the enoxaparin arm experienced clinically relevant bleeding vs. 2.8% of patients in the rivaroxaban group (relative RR=2.3; P<.0001). Similarly at 35 days, 1.7% of patients in the enoxaparin group had clinically relevant bleeding vs. 4.1% of patients in the rivaroxaban group (relative RR=2.5; P<.0001). According to Cohen, rates of liver and CV events were similar in both groups.

“We’ve shown that we have an effective drug; we have an ongoing problem and we have to look carefully at the bleeding and see if we can work out why this occurred and whether there are any groups that can benefit,” Cohen said. – by Stacey L. Fisher

Disclosure: Dr. Cohen is a medical consultant for and has received honoraria, consultancy fees and clinical trial funding from Astellas, Astra Zeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, GSK, Johnson and Johnson, Mitsubishi Pharma, Pfizer, Sanofi-Aventis, Schering Plough and Takeda. The trial was funded by Bayer HealthCare, Johnson and Johnson Pharmaceutical Research and Development, LLC.

For more information:

Cohen A. LBCT IV Session 3015. Presented at: ACC 60th Annual Scientific Sessions; April 2-5, 2011; New Orleans.

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